The Cincinnati Comprehensive Sickle Cell Center offers a program that integrates state-of-the-art clinical care with cutting-edge research - basic, translational, clinical, psychological, and health outcomes - to improve the lives of those affected by sickle cell disease (SCD). A Collaborative Phase l/ll Clinical Trial addresses inflammation as an important component of SCD to test the chronic use of an anti-inflammatory drug, Zileuton. A Patient Services Research Project will assess barriers to adherence with treatment in pediatric patients and design individualized approaches to improve compliance. A Basic Science Research Project will use innovative methods of gene transfer and RNA interference to address the mechanisms of pathological dehydration of sickle cells and will explore the therapeutic potential of this approach. A Translational Research Project will build on unique infrastructure and expertise in gene therapy trials at Cincinnati Children's Hospital Medical Center to optimize novel lentivirus vectors for safe and efficacious correction of human SCD phenotype and to perform clinical studies critical for developing a phase l/ll gene therapy trial. These efforts are supported by a Clinical Core caring for 265 pediatric patients and 195 adults in Cincinnati, and by affiliated sites with experienced clinical investigators who care for an additional 387 adults at Ohio State University and the University of South Alabama. A Patient Services Core, based at CCHMC, serves the psychosocial needs of patients and families by coordinating and assisting a large staff of professionals supported by the affiliated hospitals. An innovative program to facilitate transition from pediatric to adult care based on the primary care concept of a "medical home" will be conducted in collaboration with the University of Cincinnati Internal Medicine/Pediatrics Program. Our dedication to the future of sickle cell patients includes a firm commitment to training a new generation of academicians through the Sickle Cell Scholars Program. Lay Summary: The Cincinnati Comprehensive Sickle Cell Center provides clinical care for sickle cell disease (SCD) and basic and clinical research to develop new treatments. A multi-center trial is proposed to test if an anti-inflammatory drug can reduce inflammation in SCD. Two projects use gene transfer into blood stem cells to study ways to improve the function of sickle cells. Research is proposed to improve the adherence of SCD patients with treatment. These projects are supported by clinical facilities caring for almost 850 patients, who have the option of participating in clinical studies.